Biomedical subjects
T W O'Connor
Publications and source records attributed to T W O'Connor.
Heterogeneous X-ray survival characteristics of lymphocytes in prolymphocytic leukaemia: mathematical analysis distinguishing delayed cell death and true radioresistance.
The survival of non-dividing (G0) leukaemic lymphocytes in culture is generally too short for their radiosensitivity to be quantitatively assessed, since lethally X-irradiated cells may show a long delay before manifestations of cell death ("interphase death") are seen. Counts of surviving cells will therefore include both lethally-hit cells (apparent survivors), and real survivors which have not been lethally hit. Death rates of irradiated leukaemic and normal cells show great variation between individuals, so that comparisons of radiosensitivity between different cell populations based on surviving cell counts at a single time-point are invalid. In this study the supposed radioresistance of prolymphocytic leukaemia lymphocytes was examined in 6 patients with B-cell disease. Survival curves were plotted from serial observations made over several days after graded X-irradiation (0-1000 cGy). We attempted to interpret these radiation responses in terms of their dose dependence (intrinsic radiosensitivity) and time dependence (cell death rate) characteristics using the best-fitting of four mathematical models, all based on classical "single-hit" target theory. The apparent radioresistance shown in 4 cases could be explained by very slow death rates (T1/2 values 55-205 h) of cells proving otherwise radiosensitive (D37 values 38-123 cGy). Genuine radioresistance was found in only 1 case (actual D37 value above 2000 cGy). By ignoring delayed cell death in clinical assessments, pathological lymphocytes could be mistakenly categorised as resistant to elimination by radiotherapy.
Compliance devices preferred by elderly patients.
Many elderly patients take several medications for chronic conditions, a situation which causes problems in compliance with drug regimens. This study surveyed patients' preferences among four devices designed to make compliance easier: rub-off reminder labels, medication organizer trays, a container cap with a modified alarm clock, and a digital elapsed timer. Thirty-one enrolled patients used each device for one month then reported their ratings of four device attributes--clarity of directions for use, ease of use, convenience, and effectiveness in preventing dosing errors. The patients showed a strong preference for the medication organizer tray and generally preferred less-complex devices to those that were more difficult to learn to use.
Simplified quantitative estimation in vitro of lymphocyte radiosensitivity applied to patients with chronic lymphocytic leukaemia.
Lymphocyte survival changes observed at 1, 2 and 3 days as responses to 3 doses of ionising radiation in vitro (40, 100, and 500 cGy) are analysed by computer according to a simple (single cell population) mathematical model. Intrinsic radiosensitivity, the susceptibility to lethal injury, which is expressed as the D37 value (the radiation dose permitting 37% survival), is estimated separately from the kinetics of subsequent death of lethally-irradiated cells (expressed as their half-life, or t1/2 value). Among the 35 patients with B-cell CLL studied (15 were never treated), both parameters varied widely and independently of one another. t1/2 ranged from 9-200 h and above, D37 from 14-500 cGy or above. Twenty-three patients were deemed 'radiosensitive' (D37 below 110 cGy). D37 level did not correlate with treatment status, mode of treatment, clinical staging (Rai) or lymphocyte count. With some exceptions, D37 remained relatively constant for individual patients with increasing duration of disease or alterations in treatment status. The assay method may prove useful as an aid in predicting response to low-dose splenic irradiation (SI) in CLL.
Preoperative AIDS testing.
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Do patients have the right to infect their doctor?
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Phorbol ester-induced loss of colchicine ultrasensitivity in chronic lymphocytic leukaemia lymphocytes.
On exposure to the phorbol ester 12-O-tetradecanoyl-13-acetate (TPA) the pathological (non-dividing) lymphocytes of B-cell chronic lymphocytic leukaemia (CLL) lose their characteristic ultrasensitivity to the cytocidal action of colchicine in vitro. They are no longer killed in 1 day by the drug at 10(-6)M-concentration. The effect was the same whether the cells were incubated in the continuous presence of TPA, or subjected instead to pulse-treatment with it (for as little as 5 min.). Colchicine at one thousand times greater concentration was now needed to kill the cells. CLL lymphocytes already primed to undergo interphase death by pretreatment with colchicine could be prevented from doing so by early addition of TPA. A marked proportion of those CLL lymphocytes destined to undergo early spontaneous death in vitro in the absence of colchicine could be prevented from doing so by TPA. The loss of colchicine ultrasensitivity applied to cells which had not yet undergone TPA-induced morphological transformation to blast-like cells or differentiation to cells containing abundant cytoplasmic immunoglobulins (CIg). These transformed cells materialised in greatest incidence (70-80%) after 3 days of culture, an observation in agreement with others workers.
Colchicine ultrasensitivity of lymphocytes in chronic lymphocytic leukaemia.
It has been previously reported that, in comparison with normal lymphocytes, the lymphocytes in chronic lymphocytic leukaemia (CLL) are ultrasensitive in culture to the cytocidal action of colchicine. In this report the results of 240 colchicine studies in 87 patients with CLL are presented and analysed in terms of the diagnostic, clinical and haematological significance of colchicine ultrasensitivity (CUS) in CLL. All patients with CLL showed very significantly increased CUS of lymphocytes. The CUS did not vary with clinical and haematological status or time and only very rarely with treatment. There was no correlation between % CUS and subsequent course or survival. The results in CLL and in other forms of lymphocytosis and in non-Hodgkin's lymphoma are compared. It is concluded that the test is of considerable diagnostic value, particularly in identifying low-count and treated CLL and in the exclusion of non-CLL lymphocytosis. It appears to have no prognostic value but may have future application in monitoring treatment which selectively eliminates the abnormal cell population.
A historical review of reversed gastric tube esophagoplasty.
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Pseudomembranous colitis with sparing of transplanted colon.
There is strong evidence that pseudomembranous colitis (PMC) is caused by the toxin of Clostridium difficile. A case of PMC which occurred in a patient who underwent colon interposition for a benign oesophageal stricture is presented, which had all the features of a florid PMC, but the changes were confined to the normally sited colon, and did not occur in the interposed loop. No similar case report could be found in the literature. This case is in accord with the view that PMC is produced by the toxin of local faecal bacteria, and its occurrence is precluded by removal of the colon from the faecal stream.
Pseudomembranous enterocolitis: a historical and clinical review.
Pseudomembranous enterocolitis (PMEC) was first documented in 1893. Since this initial description, confusion has reigned in the medical literature concerning its nature and differentiation from such entities as necrotizing enterocolitis and staphylococcal enterocolitis. Since the 1950s, volumes have been written on PMEC and its association with a multitude of different antibiotics. PMEC has generally been used as somewhat of a "wastebasket" designation, being applied to any postoperative patient who develops significant diarrhea while on broad-spectrum antibiotics. More recently, a resurgence of interest in PMEC has led to its recognition as a specific disease entity and to a greater understanding of its etiology. The current review traces the history of PMEC, distinguishes if from similar disease processes, and describes its clinical presentation, diagnosis, and management. PMEC is particularly distinguished from antibiotic-associated diarrhea and certain forms of antibiotic-associated colitis.
Late development of colorectal cancer subsequent to pelvic irradiation.
Two cases of irradiation-associated carcinoma of the colon are reported and the literature reviewed. The clinical courses and operative difficulties in treating these patients are emphasized. The necessity for life-long follow-up examinations with proctoscopic and barium-enema evaluations in high-risk patients is stressed. Irradiation-associated carcinoma of the colon occurs almost exclusively in women, but should be investigated in patients of either sex who live for long periods after pelvic irradiation.
Abdominal drainage: a clinical review.
A review of the indications for, and technique of, abdominal drainage is presented. An analysis is made of the physical characteristics of the commonly used types of drains. Evidence is presented that abdominal drains, although sometimes life-saving, are potentially harmfully and should be used only when a clear indication is present. When drainage is employed, it should be of the most efficient, closed type, and the drain should be removed at the earliest safe time after operation.
Vascular dysphagia: cancer is not always the culprit.
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Try a telephone diverter for after hours calls.
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Cell studies in prolymphocytic leukaemia.
A case of prolymphocytic leukaemia, showing several features not yet reported in this disease, is reported. The majority of lymphocytes in the peripheral blood and bone marrow had markers of both B- and T-lymphocytes. The simultaneous presence of receptors for sheep RBC and surface immunoglobulins on individual cells was demonstrated and the endogenous origin of these markers was established. The lymphocytes had some of the functional characteristics seen in chronic lymphocytic leukaemia (CCL). In vitro cell death in the presence of colchicine (colchicine ultrasensitivity) and polystyrene bead column retention were of the same order as seen in CLL. In contrast with the findings in CLL, these cells were markedly radioresistant in vitro. The dominant clinical features--anaemia and constitutional symptoms--appeared to be related to hypersplenism associated with massive splenomegaly. The relevance of these findings is discussed.
Letter: Colchicine sensitivity as a test for leukemic lymphocytes.
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